A national sample of 289 Finnish adopted-away offspring of 263 schizophrenic mothers has been identified. Records indicated that 195 of these offspring of 180 biologic index mothers were placed in an unrelated Finnish family during their first 5 years of life and are at risk for schizophrenia. These adoptive index families were combined with matched adoptive control families for extensive interviewing and testing, with interviewers blind as to diagnosis of biologic mothers. Preliminary results from 96 pairs of index and control adoptive families support the hypothesis that "genetic" and "environmental rearing" factors interact in those adoptees who have become schizophrenic and severely disturbed. In order to establish the limitations and implications of these findings, this proposal requests support for a collaborative program between the University of Rochester and Oulu University, Finland, that will combine adoption and risk research strategies. Under Finnish grant support, field work will continue with adoptive families, including a unique subsample of 64 index cases plus controls available for initial prospective study when adoptees were less than 20 years old. The proposed tasks under NIMH support are: data collection from index and control biologic relatives including structured interviews for diagnostic assessments with RDC, DSM-III, and Scandinavian criteria; Rorschach, MMPI, and WAIS testing for independent scoring; and evaluation of illness severity, personality functioning, deficit symptoms, social and work functioning, and psychiatric family history. Information about the pregnancy, delivery, and early infancy will be obtained from the biologic family members and from obstetrical and baby clinic records. Ratings and data reduction from tape-recorded interviews and tests previously obtained from adoptive families are planned to assess problem-solving and communication patterns, and other aspects of the adoptive rearing environment. Inter-rater reliability checks are planned. Comprehensive model building will guide data analysis for assessing hypotheses of joint effects of genotype and environment; data analysis and interpretation also will be concerned with methodologic artifacts. Assortative mating in the biologic parents will be given special attention, with a fresh evaluation of the genetic boundaries of the schizophrenia spectrum. The groundwork will be established for later assessment of environmental direction-of-effects by giving special attention to the subsample of adoptive families with young adoptees, to be followed up as they pass through the age of risk for schizophrenia.